Scientists at Sanford Burnham Prebys Medical Discovery Institute have published findings that challenge a long-held assumption about how cells manage waste as people get older. The study, published in the journal Aging Cell on September 27, 2026, indicates that cellular recycling does not follow a uniform downward trajectory throughout the body.
Autophagy is the natural cleanup system cells use to collect defective proteins and other waste, breaking them down into reusable components. For years, researchers have considered declining autophagy a hallmark of aging, linking problems with this process to cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The new data suggests the reality is far more complex.
Cell-Specific Changes in Cellular Recycling
To understand the relationship between aging and autophagy, the research team collected blood and skin samples from volunteers aged 23 to 72. All participants reported having no chronic medical conditions. The team also converted some skin cells into induced neurons to examine recycling in three distinct cell types.
The analysis revealed that autophagic activity changes were not universal. In skin cells from male participants, recycling activity decreased as age increased. In female skin cells, it remained relatively stable. Meanwhile, induced neurons derived from female participants showed an increase in autophagy with age.
Caroline Kumsta, PhD, assistant professor in the Center for Cardiovascular and Muscular Diseases at Sanford Burnham Prebys, noted that the evidence for a simple decline in humans has been thin. “We commonly see people cite this idea that autophagy declines with age, but the actual evidence for this in humans is very thin,” Kumsta said. “Rather, cellular recycling rates are altered differently with age in each of the cell types, and differently by sex in each of the cell types.”
The study also found that gene expression levels did not reliably predict actual recycling rates. Cells with higher or lower levels of autophagy gene expression did not necessarily show corresponding differences in their measured recycling activity. This discrepancy warns researchers against relying solely on static transcription measures to infer cellular health.
Physical Health and Exercise Implications
The researchers investigated whether differences in autophagy were associated with physical health and performance. They found that higher levels of cellular recycling may have different implications for younger and older adults. Among participants aged 70 and older, greater autophagy activity was associated with poorer measures of physical function across all three cell types studied.
In blood cells, higher autophagy was linked to lower aerobic fitness. In skin cells, it was associated with a higher body mass index. In induced neurons, increased recycling activity was connected to weaker grip strength, lower metabolism, and a higher resting heart rate. These associations suggest that increased autophagy is not necessarily a sign of healthier aging in later life.
The team also explored whether physical activity could influence autophagy in older adults. In a small pilot study, five participants between the ages of 77 and 88 completed a gentle exercise program lasting 12 weeks. The activities focused on reducing the risk of falls. Preliminary results suggested that exercise could lower autophagy activity in blood cells toward levels more typical of younger adults. Participants also showed improvements in physical performance.
Tatiana Moreno, PhD, lead author of the study, emphasized the need for nuance in future therapies. “Autophagy and aging are so much more nuanced than previously assumed,” Moreno said. “To better translate autophagy research discoveries into potential therapies, we really need to understand what is happening on a cell-specific level and how it is affected by sex and age.”
The Kumsta laboratory has received a pilot grant from the Altman Clinical and Translational Research Institute at the University of California San Diego. The team is now working with the Exercise and Physical Activity Resource Center at UC San Diego on larger studies involving more participants and improved testing methods to examine how physical activity affects autophagy and physical function.
Source: ScienceDaily
